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Biomedical subjects

R R Berardi

Publications and source records attributed to R R Berardi.

At least 19 recordsLinked to original sources
PubMed2001

Proton pump inhibition. An effective, safe approach to GERD management.

Prescribed worldwide to treat gastroesophageal reflux disease (GERD), the proton pump inhibitors (PPIs) not only relieve acid reflux-related symptoms more rapidly than standard-dose or high-dose histamine2 receptor antagonists but also accelerate the rate of esophageal healing. Five PPIs--omeprazole, esomeprazole, lansoprazole, rabeprazole, and pantoprazole--are currently labeled by the Food and Drug Administration. These agents share a common mechanism of action and rarely exhibit clinically important interactions with other hepatically metabolized medications or pH-dependent drugs. Except for lingering concern about their long-term use in Helicobacter pylori-positive patients, the PPIs produce relatively few adverse effects when administered for the short or long term. Because primary care physicians are generally the first to treat patients with GERD, they may find it helpful to expand their knowledge of the pharmacologic effects of the PPIs. With an eye toward this end, Dr Berardi presents a cogent overview of PPI pharmacodynamics, pharmacokinetics, efficacy, drug interactions, and safety.

Anti-Ulcer Agents↗
PubMed2000

A critical evaluation of proton pump inhibitors in the treatment of gastroesophageal reflux disease.

Proton pump inhibitors (PPIs) are the drugs of choice for treating gastroesophageal reflux disease (GERD). Their superiority to histamine2 receptor antagonists (H2RAs), cisapride, and sucralfate is directly related to their potent and prolonged suppression of gastric acid. The PPIs provide the most rapid relief of GERD symptoms and esophageal healing when compared with standard- or high-dose H2RAs or cisapride. Their superiority over H2RAs has also been demonstrated when used in maintaining esophageal healing and symptom relief. The cost effectiveness of standard-dose PPIs in the treatment of GERD has been well documented. High-dose PPI therapy may benefit patients with atypical GERD symptoms and may also be cost effective. Four PPIs are available in the United States: omeprazole, lansoprazole, rabeprazole, and pantoprazole. All 4 PPIs, when used in recommended dosages, are very effective for the acute and chronic treatment of GERD and demonstrate similar short- and long-term safety profiles. Subtle differences appear to exist, some of which are based on data obtained in vitro or from healthy volunteer studies and others on trends or relatively minor differences observed in selective clinical trials. In most cases, experience has not yet confirmed the clinical importance of these potential differences. The selection of a preferred PPI for a hospital or managed care formulary will most likely be based on the acquisition cost of the drug.

Anti-Ulcer Agents↗
PubMed1996

Use of zinc tolerance test and 24-hour urinary zinc content to assess oral zinc absorption.

OBJECTIVES: The sensitivity of one plasma and two urinary methods to assess zinc absorption after oral dosing were compared over the dose range of 10 to 100 mg. METHODS: Eleven healthy subjects participated in this four-way crossover design study. After an overnight fast, the subjects received a single oral dose of zinc acetate corresponding to 10, 25, 50, or 100 mg of elemental zinc. Plasma zinc concentrations were measured at baseline (pre-zinc administration) and hourly intervals post-zinc administration for 9 hours. Urine was collected for 24 hours prior to and for 24 hours after zinc administration. During this 48-hour period, subjects consumed an isocaloric, caffeine-free diet containing 18 mg of elemental zinc per day. RESULTS: The area under the plasma zinc concentration versus time curve (PZAUC) increased linearly with doses between 10 and 50 mg, then flattened out. By contrast, urinary zinc excretion was approximately linear with doses in the 25 to 100 mg range, but no differences were observed in urinary zinc excretion after doses of 10 and 25 mg. CONCLUSIONS: Plasma zinc concentration is a useful method of evaluating oral zinc absorption from doses of 10 to 50 mg. Urinary zinc excretion is an alternative method of assessing zinc absorption, particularly when doses of 50 to 100 mg of elemental zinc are administered.

Administration, Oral↗
PubMed1995

Intravenous histamine H2-receptor antagonists and parenteral nutrition: patterns of use.

Patterns of use of i.v. histamine h2-receptor antagonists (H2RAs) and parenteral nutrient solutions in patients receiving both given separately or as admixtures were studied. Consecutive adult patients at a university teaching hospital were placed in an "admixed group," consisting of all those who received an i.v. H2RA as a parenteral nutrient solution additive, or a "nonadmixed group," consisting of all those who received an i.v. H2RA and a parenteral nutrient solution as separate infusions. Data were collected for many variables, including interruptions in therapy, route and method of administration, indication for use, total daily dose of H2RA, patient demographic data, and any additional anti-ulcer drugs prescribed. A total of 128 patients received 158 regimens of therapy, 60 regimens in the admixed group and 98 in the nonadmixed group. There was at least one interruption in i.v. H2RA therapy for 32% of the admixed-group regimens and 33% of the nonadmixed-group regimens. When an interruption occurred, patients in the admixed group missed an average of 40% of their daily H2RA dose, compared with 53% for the nonadmixed group. No alternative anti-ulcer drug was given on 10 (23%) of the 42 days when intensive care patients had an interruption in H2RA therapy, versus 33 (55%) of the 60 days of H2RA interruption for non-intensive-care patients. Interruptions in i.v. H2RA therapy occurred more frequently when the H2RA was a component of the nutrient solution than when it was given as a separate infusion. Supplemental anti-ulcer therapy was typically not provided during interruptions in H2RA therapy, regardless of the method of administration.

Adult↗
PubMed1994

The effect of competitive and non-linear plasma protein binding on the stereoselective disposition and metabolic inversion of ibuprofen in healthy subjects.

The stereoselective disposition and metabolic inversion of ibuprofen were studied in 12 healthy subjects under conditions of competitive and non-linear plasma protein binding. Each subject received each of four oral treatments according to a Latin-square design: 300 mg R(-)-ibuprofen, 300 mg S(+)-ibuprofen, 300 mg R(-)(-)+300 mg S(+)-ibuprofen, and 300 mg R(-)(-)+600 mg S(+)-ibuprofen. For a given treatment, the partial clearance of S(+)-ibuprofen was greater than that of R(-)-ibuprofen for all stereoisomeric drug species. Likewise, the unbound partial clearances of S(+)-ibuprofen were greater for most stereoisomeric drug species. There was also less difference among treatment groups when partial clearances were referenced to unbound as opposed to total plasma concentrations of enantiomer. The unbound intrinsic clearance and fractional inversion of R(-)-ibuprofen were unchanged across the four treatments, and chiral inversion was systemic, averaging 69%. In conclusion, stereoselective differences exist for the partial and composite clearances of R(-)- and S(+)-ibuprofen even when corrected for differences in plasma protein binding. However, differences among treatment groups for a particular elimination pathway are largely due to ibuprofen's non-linear binding.

Administration, Oral↗
PubMed1994

pH-related changes in the absorption of dipyridamole in the elderly.

The bioavailability of dipyridamole, a poorly soluble weak base, was evaluated in 11 healthy, older subjects (> or = 65 years), 6 with a low fasting gastric pH (control) and 5 with a fasting gastric pH > 5 (achlorhydric), in a randomized, crossover design. Subjects received 50 mg dipyridamole as a single oral dose both with and without pretreatment with 40 mg famotidine (control subjects) or 1360 mg glutamic acid HCl (achlorhydric subjects). Gastric pH was monitored by Heidelberg radiotelemetric capsule. Gastric emptying of 99mTc-radiolabeled orange juice was measured. Gastric pH appeared to be a primary determinant in dipyridamole absorption in the elderly. Elevated gastric pH resulted in compromised dipyridamole absorption compared to low-gastric pH conditions in all cases. The administration of glutamic acid hydrochloride to achlorhydric subjects prior to the dose of dipyridamole corrected for the decreased Cmax and AUC(0-36) exhibited in achlorhydric subjects without pretreatment. Tmax and ka were slower in achlorhydrics, although pretreatment with glutamic acid HCl tended to normalize these parameters. Based on these results, it would be beneficial for achlorhydrics to take glutamic acid hydrochloride prior to taking dipyridamole and other medications which need a low gastric pH for complete absorption. The administration of 40 mg famotidine was successful in elevating the gastric pH to > 5 in all subjects and maintained it at > 5 for at least 3 hr in all subjects tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Achlorhydria↗
PubMed1994

In vivo interaction of ketoconazole and sucralfate in healthy volunteers.

Absorption of ketoconazole is impaired in subjects with an increased gastric pH due to administration of antacids, H2-receptor antagonists, proton pump inhibitors, or the presence of hypochlorhydria. Sucralfate could provide an attractive alternative in patients receiving ketoconazole who require therapy for acid-peptic disorders. Twelve healthy human volunteers were administered a single 400-mg oral dose of ketoconazole in each of three randomized treatment phases. In phase A, ketoconazole was administered orally with 240 ml of water. In phase B, ketoconazole and sucralfate (1.0 g) were administered simultaneously with 240 ml of water. In phase C, ketoconazole was administered with 240 ml of water 2 h after administration of sucralfate (1.0 g) orally with 240 ml of water. A 680-mg oral dose of glutamic acid hydrochloride was administered 10 min prior to and with each dose of ketoconazole, sucralfate, or ketoconazole plus sucralfate. Simultaneous administration of ketoconazole and sucralfate led to a significant reduction in the area under the concentration-time curve and maximal concentration of ketoconazole in serum (78.12 +/- 12.20 versus 59.32 +/- 13.61 micrograms.h/ml and 12.34 +/- 3.07 versus 8.92 +/- 2.57 micrograms/ml, respectively; P < 0.05). When ketoconazole was administered 2 h after sucralfate, the observed ketoconazole area under the concentration-time curve was not significantly decreased compared with that of ketoconazole alone. The time to maximal concentrations in serum and the ketoconazole elimination rate constant were not significantly different in any of the three treatment phases. In patients receiving concurrent administration of ketoconazole and sucralfate, doses should be separated by at least 2 h.

Absorption↗
PubMed1993

High-molecular-weight hydroxypropylmethylcellulose. A cholesterol-lowering agent.

BACKGROUND: We assessed the efficacy of a high-molecular-weight hydroxypropylmethylcellulose (K8515) as a cholesterol-lowering agent, the dose-response profile of its action, and the ability of adult subjects to tolerate its ingestion at effective doses. METHODS: These studies were conducted at the Clinical Research Center of The University of Michigan Hospitals, Ann Arbor. Efficacy was assessed in 10 normal and 12 mildly hyperlipidemic subjects in double-blind, randomized crossover trials of 1 and 2 weeks' duration, respectively. The dose-response profile was studied in 12 mildly hypercholesterolemic subjects in a nonrandomized control trial with doses given in escalating order. Tolerance was assessed by a questionnaire of adverse effects and bowel movement habits in all subjects. RESULTS: We found that 10 g of K8515 ingested in a prehydrated form three times a day with meals lowered total cholesterol levels by an average of 1.45 mmol/L (56 mg/dL) (32%) in normal subjects within 1 week. In two studies in subjects with mildly elevated cholesterol levels (with entry levels ranging from 5.35 mmol/L [207 mg/dL] to 6.70 mmol/L [260 mg/dL]), average reductions of 1.00 mmol/L (39 mg/dL) (18%) and 1.15 mmol/L (45 mg/dL) (20%) were observed within the same period. The effect was primarily due to a reduction in low-density lipoprotein cholesterol levels. Low-density lipoprotein levels in normal subjects were an average of 1.10 mmol/L (42 mg/dL) (38%) lower after a week of 10 g of K8515 three times a day with meals, and in the two studies in subjects with mild hyperlipidemia, the reductions in low-density lipoprotein levels after 1 week were 0.95 mmol/L (37 mg/dL) (23%) and 1.05 mmol/L (40 mg/dL) (25%). Although there was a tendency for high-density lipoprotein cholesterol levels to decrease, this was significant only in normal subjects. Decreases in cholesterol levels were not accompanied by any rise in triglyceride levels. Dose-response studies in those with mildly elevated cholesterol levels indicated that it is possible to achieve a 15% decrease in low-density lipoprotein cholesterol levels within 1 week at a dose of 6.7 g three times a day, with minimal adverse effects. CONCLUSION: These results suggest a role for high-molecular-weight hydroxypropylmethylcellulose in the clinical treatment of mild hypercholesterolemia.

Adult↗
PubMed1993

Stereoselective, competitive, and nonlinear plasma protein binding of ibuprofen enantiomers as determined in vivo in healthy subjects.

The plasma protein binding and competitive inhibition parameters of R(-)- and S(+)-ibuprofen were determined in vivo in 12 healthy subjects. Subjects participated in a 4 x 4 Latin square design in which oral solutions of drug were administered as 300 mg R(-)-ibuprofen, 300 mg S(+)-ibuprofen, 300 mg R(-)- + 300 mg S(+)-ibuprofen, and 300 mg R(-)- + 600 mg S(+)-ibuprofen. Unlabeled ibuprofen enantiomers were quantitated using a stereospecific reversed-phase HPLC assay, and plasma protein binding experiments were performed using radiolabeled 14C-enantiomers and an ultrafiltration method at 37C. At therapeutic drug concentrations, the protein binding of each enantiomer was greater than 99%. Furthermore, the binding of ibuprofen enantiomers was stereoselective and mutually competitive, as well as nonlinear. The bound-free data were fitted to a model in which the non-linearity of plasma protein binding and competition between enantiomers for binding sites could be accommodated. There were substantial differences in the affinity of ibuprofen enantiomers for protein binding sites (RP2 = 0.358 +/- 0.185 vs. SP2 = 0.979 +/- 0.501 micrograms/ml; mean +/- SD) but no differences in their binding capacity (RP1 = 160 +/- 86 vs. SP1 = 161 +/- 63 micrograms/ml). Although statistically significant, the differences in competitive inhibition parameters were more modest (SKI = 0.661 +/- 0.363 vs. RKI = 0.436 +/- 0.210 micrograms/ml). As a result, the intrinsic binding (i.e., P1/P2) of R(-)-ibuprofen was greater than S(+)-ibuprofen, and the unbound fraction was significantly greater for S-enantiomer vs. R-enantiomer after a given dose of R-ibuprofen or racemate.

Adult↗
PubMed1993

Peptic ulcer disease: an update.

Peptic ulcers can develop when there is an imbalance between gastric acid secretion and gastroduodenal mucosal defense. Investigators are looking at the role of Helicobacter pylori in the development of peptic ulcer disease; eradication of the microorganism may reduce recurrence. Approved drug therapy includes H2-receptor antagonists, omeprazole, sucralfate, and antacids. Recommendations for treating and counseling patients are provided.

Antacids↗
PubMed1993

Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women.

Gastric and duodenal pH levels were measured in 79 healthy, elderly men and women (mean +/- SD = 71 +/- 5 years) under both fasted and fed conditions using the Heidelberg capsule technique. The pH was recorded for 1 hr in the fasted state, a standard liquid and solid meal of 1000 cal was given over 30 min, then the pH was measured for 4 hr postprandially. Results are given as medians and interquartile ranges: fasted gastric pH, 1.3 (1.1-1.6); gastric pH during the meal, 4.9 (3.9-5.5); fasted duodenal pH, 6.5 (6.2-6.7); and duodenal pH during the meal, 6.5 (6.4-6.7). Although fasted gastric pH, fasted duodenal pH, and duodenal pH during the meal differ statistically from those observed in young subjects, the differences are not expected to be clinically significant in terms of drug absorption for the majority of elderly subjects. Following a meal, gastric pH decreased from a peak pH of 6.2 (5.8-6.7) to pH 2.0 within 4 hr in most subjects. This rate of return was considerably slower than in young, healthy subjects. Nine subjects (11%) had a median fasted gastric pH > 5.0, and in five of these subjects the median pH remained > 5.0 postprandially. In this group, drugs and dosage forms which require an acidic environment for dissolution or release may be poorly assimilated.

Achlorhydria↗
PubMed1992

Absorption of flurbiprofen in the fed and fasted states.

The oral absorption of flurbiprofen, an antiinflammatory nonsteroidal compound, was compared in the fasted vs the fed state. When ingested as an aqueous solution of the sodium salt, absorption kinetics followed a monoexponential pattern in half of the subjects and a bimodal pattern with a lag time before the onset of the second phase of absorption in the other half of the subjects. When ingested in the free acid form as a tablet either with water (fasted state) or with water 15 min after 330 ml of apple juice (fed state), flurbiprofen absorption was always bimodal, and the lag time before the onset of the second phase was shown to be dependent on the gastric emptying time (r = 0.623, P less than 0.01). The gastric emptying times were significantly longer when the drug was administered in the fed state (average GET = 57 min in the fasted state and 102 min in the fed state; P less than 0.01). These results suggest that gastric emptying effects are one important way in which absorption of drugs can be affected by meal intake.

Administration, Oral↗
PubMed1991

Evaluation of direct pharmacist intervention on conversion from parenteral to oral histamine H2-receptor antagonist therapy.

A program in which pharmacists were authorized to change parenteral histamine H2-receptor antagonist (H2RA) therapy to the oral route without first contacting the prescriber was evaluated on cost and appropriateness of use of the parenteral route. Parenteral therapy was received by 264 and 244 patients in the study and comparison groups, respectively. Length of parenteral H2RA therapy was less in the study group (4.8 vs. 7.5 d) as was length of total (parenteral + oral) therapy (8.4 vs. 12.1 d). Parenteral H2RA drug acquisition savings were $6225 in the six-week study period or $53,950 when annualized. Decreased oral therapy contributed additional savings. There was a significant decrease in the number of inappropriate parenteral doses of ranitidine per patient, the drug used in more than 80 percent of the patients. In addition to the direct effect of pharmacists' interventions, there appeared to be an indirect effect of the program, as physicians initiated route of administration changes on their own.

Administration, Oral↗
PubMed1991

Modification of gastric pH with oral glutamic acid hydrochloride.

The extent to which oral glutamic acid hydrochloride decreases mean gastric pH in fasting persons with and without simulated hypochlorhydria was studied. Healthy nonsmoking men were randomly assigned to one of two drug regimens followed by the other regimen after a one-week washout period. In regimen 1 the fasting subjects received two 680-mg doses of glutamic acid hydrochloride given 10 minutes apart. Regimen 2 was the same, except that an oral dose of ranitidine 300 mg (as the hydrochloride salt) was administered one to two hours before the first dose of glutamic acid hydrochloride to simulate hypochlorhydria. Gastric pH was monitored radiotelemetrically before and after glutamic acid hydrochloride administration by using the Heidelberg capsule technique. Six men 20 to 28 years of age participated in the study. For regimen 1, the gastric pH before glutamic acid hydrochloride was given was not significantly different from that after administration (grand medians, 1.4 and 1.3, respectively). In regimen 2, the median gastric pH increased to greater than 4.0 within two hours after ranitidine treatment. Median gastric pH after the second dose of glutamic acid hydrochloride was significantly lower than before the first dose (grand medians, 1.6 and 6.2, respectively). The time to minimum pH was 2 to 15 minutes, and pH remained less than 3.0 for a mean of 45 minutes. Glutamic acid hydrochloride alone did not decrease fasting gastric pH, but it significantly reduced pH in subjects with simulated hypochlorhydria produced by orally administered ranitidine.

Acid-Base Equilibrium↗
PubMed1990

Upper gastrointestinal (GI) pH in young, healthy men and women.

The pH in the upper gastrointestinal tract of young, healthy men and women was measured in the fasting state and after administration of a standard solid and liquid meal. Calibrated Heidelberg capsules were used to record the pH continuously over the study period of approximately 6 hr. In the fasted state, the median gastric pH was 1.7 and the median duodenal pH was 6.1. When the meal was administered the gastric pH climbed briefly to a median peak value of 6.7, then declined gradually back to the fasted state value over a period of less than 2 hr. In contrast to the pH behavior in the stomach, feeding a meal caused a reduction in the median duodenal pH to 5.4. In addition, there was considerable fluctuation in the postprandial duodenal pH on an intrasubject basis. The pH in the duodenum did not return to fasted state values within the 4-hr postprandial observation period. There was no tendency for the duodenal pH to be related to the gastric pH in either the fed or fasted phases of the study. Furthermore, pH in the upper GI tract of young, healthy subjects appears to be independent of gender. The differences in upper GI pH between the fasted and the fed state are discussed in terms of dosage form performance and absorption for orally administered drugs.

Adult↗